Genetic and Molecular Signaling for Cellular Differentiation and Skeletogenesis

Description

The central focus of our laboratory is to understand the molecular mechanisms that govern the formation and remodeling of skeletal tissues such as Cartilage, Bone, Teeth and Tendon. Cellular differentiation involves the stepwise establishment of specific genetic programs in proliferating cell lineages. We are exploring the signalling role of runt related transcription factor (Runx), in the coordinated regulation of various cell types (Chondrocyte, Osteoblast, Odontoblast) during skeletogenesis.
Runx factors are heterodimers formed by α and β subunit and are essential for embryonic development. In mammals three genes encode α subunits (Runx1, 2 and 3) that recognize the same DNA sequences in target gene promoters yet exhibit distinct and non-redundant biological functions. Runx1 is required for definitive hematopoiesis and is frequently mutated in human leukemia. Runx2 is required for osteogenesis and in human mutations of the Runx2 gene are associated with cleidocranial dysplasia, an autosomal dominant skeletal disorder characterized by clavicular and pelvic anomalies, multiple supernumerary teeth, and a sever delay in closure of the fontanels. Runx3 controls neurogenesis, development and proliferation of the gastric epithelium and is frequently silenced in human gastric cancer.
Runx2 knock-in and knock-out mouse models are lethal and show a complete absence of both intramembranous and endochondral ossification. Our lab utilizes conditional null model with biochemical, cellular, genetic and molecular approaches to identify molecular pathways during post-natal bone formation, bone remodeling, fracture healing, osteoporosis, osteoarthritis metabolic diseases (diabetes, obesity) and aging.